The principal aim of these studies is to identify cell types in the humoral immune system which are developmentally intermediate between uncommitted hemopoietic stem cells and functional B lymphocytes. This is being attempted by means of new monoclonal antibodies directed at cell surface antigens used in conjunction with in vivo and in vitro assay systems in which stem cells and committed precursor cells give rise to B cells. Partially immunodeficient CBA/N mice are being exploited in these studies because they have no B cells which can be detected with a cloning assay but provide normal microenvironments for formation of such functional B cells from the hemopoietic cells of normal, histocompatible donors. It is hoped that developmental relationships between various precursors will be revealed as well as the kinetics and inductive interactions associated with early differentiative events. Related investigations are being conducted with established cell lines which under appropriate conditions undergo some of the maturation steps achieved by normal B lineage cells.